Oxygen Regulates Vascular Endothelial Growth Factor-Mediated Vasculogenesis and Tubulogenesis

AbstractTo determine whether low oxygen is a stimulus for endothelial cell differentiation and vascular development in the kidney, we examined the effect of low oxygen on rat metanephric organ culture, a model known to recapitulate nephrogenesis in the absence of vessels. After 6 days in culture in standard (20% O2) or low oxygen (1–3% O2) conditions, metanephric kidney growth and morphology were assessed by DNA measurement, and light and electron microscopy. DNA content was higher in 3% O2-treated explants (2.5 ± 0.17 μg/kidney,n= 9) than in 20% O2explants (1.5 ± 0.09 μg/kidney,n= 9),P< 0.05. Low oxygen induced proliferation of tubular epithelial cells, resulting in enhanced number of tubules of similar size. Endothelial cells forming capillaries were localized in 3% O2explants by light and electron microscopy and by immunocytochemistry using endothelial cell markers. Flt-1, Flk-1, and ACE-containing cells were detected in 3% O2-treated explants, whereas 20% O2explants were virtually negative. VEGF mRNA levels were 10-fold higher in 3% O2-treated explants than in 20% O2-treated explants. Addition of anti-VEGF antibodies to 3% O2-treated explants prevented low oxygen-induced growth and endothelial cell differentiation and proliferation. Our data indicate that low oxygen stimulates growth by cell proliferation and induces tubulogenesis, endothelial cell differentiation, and vasculogenesis in metanephric kidneys in culture. Upregulation of VEGF expression by low oxygen and prevention of low oxygen-induced tubulogenesis and vasculogenesis by anti-VEGF antibodies indicate that these changes were mediated by VEGF. These data suggest that low oxygen is the stimulus to initiate renal vascularization

Forecasting U.S. Home Foreclosures with an Index of Internet Keyword Searches

Finding data to feed into financial and risk management models can be challenging. Many analysts attribute a lack of data or quality information as a contributing factor to the worldwide financial crises that seems to have begun in the U.S. subprime mortgage market. In this paper, a new source of data, key word search statistics recently available from Google, are applied in a experiment to develop a short-term forecasting model for the number of foreclosures in the U.S. housing market. The keyword search data significantly improves forecast of foreclosures, suggesting that this data can be useful for financial risk management. More generally, the new data source shows promise for a variety of financial and market analyses

HYPER-RESPONSIVENESS OF ALDOSTERONE TO METOCLOPRAMIDE IN ALDOSTERONISM

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73101/1/j.1365-2265.1982.tb02761.x.pd

Heavy mass expansion, light-by-light scattering and the anomalous magnetic moment of the muon

Contributions from light-by-light scattering to (g_\mu-2)/2, the anomalous magnetic moment of the muon, are mediated by the exchange of charged fermions or scalar bosons. Assuming large masses M for the virtual particles and employing the technique of large mass expansion, analytical results are obtained for virtual fermions and scalars in the form of a series in (m_\mu /M)^2. This series is well convergent even for the case M=m_\mu. For virtual fermions, the expansion confirms published analytical formulae. For virtual scalars, the result can be used to evaluate the contribution from charged pions. In this case our result confirms already available numerical evaluations, however, it is significantly more precise.Comment: revtex4, eps figure

Improved Measurement of the Positive Muon Anomalous Magnetic Moment

A new measurement of the positive muon's anomalous magnetic moment has been made at the Brookhaven Alternating Gradient Synchrotron using the direct injection of polarized muons into the superferric storage ring. The angular frequency difference omega_{a} between the angular spin precession frequency omega_{s} and the angular orbital frequency omega_{c} is measured as well as the free proton NMR frequency omega_{p}. These determine R = omega_{a} / omega_{p} = 3.707~201(19) times 10^{-3}. With mu_{mu} / mu_{p} = 3.183~345~39(10) this gives a_{mu^+} = 11~659~191(59) times 10^{-10} (pm 5 ppm), in good agreement with the previous CERN and BNL measurements for mu^+ and mu^-, and with the standard model prediction.Comment: 4 pages, 4 figures. accepted for publication in Phys. Rev. D62 Rapid Communication

Search for flavor-changing neutral currents and lepton-family-number violation in two-body D0 decays

Results of a search for the three neutral charm decays, D0 -> mu e, D0 -> mu mu, and D0 -> e e, are presented. This study was based on data collected in Experiment 789 at the Fermi National Accelerator Laboratory using 800 GeV/c proton-Au and proton-Be interactions. No evidence is found for any of the decays. Upper limits on the branching ratios, at the 90% confidence level, are obtained.Comment: 28 pages, 18 figures. Submitted to Physical Review

Effects of Large CP violating phases on g_{\m}-2 in MSSM

Effects of CP violation on the supersymmetric electro-weak correction to the anomalous magnetic moment of the muon are investigated with the most general allowed set of CP violating phases in MSSM. The analysis includes contributions from the chargino and the neutralino exchanges to the muon anomaly. The supersymmetric contributions depend only on specific combinations of CP phases. The independent set of such phases is classified. We analyse the effects of the phases under the EDM constraints and show that large CP violating phases can drastically affect the magnitude of the supersymmetric electro-weak contribution to $a_{\mu}$ and may even affect its overall sign.Comment: 26 pages Latex file including 4 figure

The choline transporter Slc44a2 controls platelet activation and thrombosis by regulating mitochondrial function

Genetic factors contribute to the risk of thrombotic diseases. Recent genome wide association studies have identified genetic loci including SLC44A2 which may regulate thrombosis. Here we show that Slc44a2 controls platelet activation and thrombosis by regulating mitochondrial energetics. We find that Slc44a2 null mice (Slc44a2(KO)) have increased bleeding times and delayed thrombosis compared to wild-type (Slc44a2(WT)) controls. Platelets from Slc44a2(KO) mice have impaired activation in response to thrombin. We discover that Slc44a2 mediates choline transport into mitochondria, where choline metabolism leads to an increase in mitochondrial oxygen consumption and ATP production. Platelets lacking Slc44a2 contain less ATP at rest, release less ATP when activated, and have an activation defect that can be rescued by exogenous ADP. Taken together, our data suggest that mitochondria require choline for maximum function, demonstrate the importance of mitochondrial metabolism to platelet activation, and reveal a mechanism by which Slc44a2 influences thrombosis

News from the Muon (g-2) Experiment at BNL

The magnetic moment anomaly a_mu = (g_mu - 2) / 2 of the positive muon has been measured at the Brookhaven Alternating Gradient Synchrotron with an uncertainty of 0.7 ppm. The new result, based on data taken in 2000, agrees well with previous measurements. Standard Model evaluations currently differ from the experimental result by 1.6 to 3.0 standard deviations.Comment: Talk presented at RADCOR - Loops and Legs 2002, Kloster Banz, Germany, September 8-13 2002, to be published in Nuclear Physics B (Proc. Suppl.); 5 pages, 3 figure

Bimodal age distribution at diagnosis in breast cancer persists across molecular and genomic classifications

Purpose: Female breast cancer demonstrates bimodal age frequency distribution patterns at diagnosis, interpretable as two main etiologic subtypes or groupings of tumors with shared risk factors. While RNA-based methods including PAM50 have identified well-established clinical subtypes, age distribution patterns at diagnosis as a proxy for etiologic subtype are not established for molecular and genomic tumor classifications. Methods: We evaluated smoothed age frequency distributions at diagnosis for Carolina Breast Cancer Study cases within immunohistochemistry-based and RNA-based expression categories. Akaike information criterion (AIC) values compared the fit of single density versus two-component mixture models. Two-component mixture models estimated the proportion of early-onset and late-onset categories by immunohistochemistry-based ER (n = 2860), and by RNA-based ESR1 and PAM50 subtype (n = 1965). PAM50 findings were validated using pooled publicly available data (n = 8103). Results: Breast cancers were best characterized by bimodal age distribution at diagnosis with incidence peaks near 45 and 65 years, regardless of molecular characteristics. However, proportional composition of early-onset and late-onset age distributions varied by molecular and genomic characteristics. Higher ER-protein and ESR1-RNA categories showed a greater proportion of late age-at-onset. Similarly, PAM50 subtypes showed a shifting age-at-onset distribution, with most pronounced early-onset and late-onset peaks found in Basal-like and Luminal A, respectively. Conclusions: Bimodal age distribution at diagnosis was detected in the Carolina Breast Cancer Study, similar to national cancer registry data. Our data support two fundamental age-defined etiologic breast cancer subtypes that persist across molecular and genomic characteristics. Better criteria to distinguish etiologic subtypes could improve understanding of breast cancer etiology and contribute to prevention efforts